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  1. Fatty Acid Conjugated Chalcones as Tubulin Polymerization Inhibitors: Design, Synthesis, QSAR, and Apoptotic and Antiproliferative Activity
    Mohamed SM, Abou-Ghadir OMF, El-Mokhtar MA, Aboraia AS, Abdel Aal AM
    J Nat Prod, 2023 May 26;86(5):1150-1158.
    PMID: 37098901 DOI: 10.1021/acs.jnatprod.2c00793
    Cancer is often associated with an aberrant increase in tubulin and microtubule activity required for cell migration, invasion, and metastasis. A new series of fatty acid conjugated chalcones have been designed as tubulin polymerization inhibitors and anticancer candidates. These conjugates were designed to harness the beneficial physicochemical properties, ease of synthesis, and tubulin inhibitory activity of two classes of natural components. New lipidated chalcones were synthesized from 4-aminoacetophenone via N-acylation followed by condensation with different aromatic aldehydes. All new compounds showed strong inhibition of tubulin polymerization and antiproliferative activity against breast and lung cancer cell lines (MCF-7 and A549) at low or sub-micromolar concentrations. A significant apoptotic effect was shown using a flow cytometry assay that corresponded to cytotoxicity against cancer cell lines, as indicated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Decanoic acid conjugates were more potent than longer lipid analogues, with the most active being more potent than the reference tubulin inhibitor, combretastatin-A4 and the anticancer drug, doxorubicin. None of the newly synthesized compounds caused any detectable cytotoxicity against the normal cell line (Wi-38) or hemolysis of red blood cells below 100 μM. It is unlikely that the new conjugates described would affect normal cells or interrupt with cell membranes due to their lipidic nature. A quantitative structure-activity relationship analysis was performed to determine the influence of 315 descriptors of the physicochemical properties of the new conjugates on their tubulin inhibitory activity. The obtained model revealed a strong correlation between the tubulin inhibitory activity of the investigated compounds and their dipole moment and degree of reactivity.
    Matched MeSH terms: Tubulin/metabolism; Tubulin Modulators/chemistry
  2. Colchicine prodrugs and codrugs: Chemistry and bioactivities
    Ghawanmeh AA, Chong KF, Sarkar SM, Bakar MA, Othaman R, Khalid RM
    Eur J Med Chem, 2018 Jan 20;144:229-242.
    PMID: 29274490 DOI: 10.1016/j.ejmech.2017.12.029
    Antimitotic colchicine possesses low therapeutic index due to high toxicity effects in non-target cell. However, diverse colchicine analogs have been derivatized as intentions for toxicity reduction and structure-activity relationship (SAR) studying. Hybrid system of colchicine structure with nontoxic biofunctional compounds modified further affords a new entity in chemical structure with enhanced activity and selectivity. Moreover, nanocarrier formulation strategies have been used for colchicine delivery. This review paper focuses on colchicine nanoformulation, chemical synthesis of colchicine prodrugs and codrugs with different linkers, highlights linker chemical nature and biological activity of synthesized compounds. Additionally, classification of colchicine prodrugs based on type of conjugates is discussed, as biopolymers prodrugs, fluorescent prodrug, metal complexes prodrug, metal-labile prodrug and bioconjugate prodrug. Finally, we briefly summarized the biological importance of colchicine nanoformulation, colchicine prodrugs and codrugs.
    Matched MeSH terms: Tubulin Modulators/pharmacology*; Tubulin Modulators/chemistry*
  3. Fulltext Phenotypic and molecular characterization of Colletotrichum species associated with anthracnose of banana (Musa spp) in Malaysia
    Intan Sakinah MA, Suzianti IV, Latiffah Z
    Genet. Mol. Res., 2014;13(2):3627-37.
    PMID: 24854442 DOI: 10.4238/2014.May.9.5
    Anthracnose caused by Colletotrichum species is a common postharvest disease of banana fruit. We investigated and identified Colletotrichum species associated with anthracnose in several local banana cultivars based on morphological characteristics and sequencing of ITS regions and of the β-tubulin gene. Thirty-eight Colletotrichum isolates were encountered in anthracnose lesions of five local banana cultivars, 'berangan', 'mas', 'awak', 'rastali', and 'nangka'. Based on morphological characteristics, 32 isolates were identified as Colletotrichum gloeosporioides and 6 isolates as C. musae. C. gloeosporioides isolates were divided into two morphotypes, with differences in colony color, shape of the conidia and growth rate. Based on ITS regions and β-tubulin sequences, 35 of the isolates were identified as C. gloeosporioides and only 3 isolates as C. musae; the percentage of similarity from BLAST ranged from 95-100% for ITS regions and 97-100% for β-tubulin. C. gloeosporioides isolates were more prevalent compared to C. musae. This is the first record of C. gloeosporioides associated with banana anthracnose in Malaysia. In a phylogenetic analysis of the combined dataset of ITS regions and β-tubulin using a maximum likelihood method, C. gloeosporioides and C. musae isolates were clearly separated into two groups. We concluded that C. gloeosporioides and C. musae isolates are associated with anthracnose in the local banana cultivars and that C. gloeosporioides is more prevalent than C. musae.
    Matched MeSH terms: Tubulin/genetics
  4. Fulltext Tubulin and Tau: Possible targets for diagnosis of Parkinson's and Alzheimer's diseases
    Salama M, Shalash A, Magdy A, Makar M, Roushdy T, Elbalkimy M, et al.
    PLoS One, 2018;13(5):e0196436.
    PMID: 29742117 DOI: 10.1371/journal.pone.0196436
    Neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by progressive neuronal loss and pathological accumulation of some proteins. Developing new biomarkers for both diseases is highly important for the early diagnosis and possible development of neuro-protective strategies. Serum antibodies (AIAs) against neuronal proteins are potential biomarkers for AD and PD that may be formed in response to their release into systemic circulation after brain damage. In the present study, two AIAs (tubulin and tau) were measured in sera of patients of PD and AD, compared to healthy controls. Results showed that both antibodies were elevated in patients with PD and AD compared to match controls. Curiously, the profile of elevation of antibodies was different in both diseases. In PD cases, tubulin and tau AIAs levels were similar. On the other hand, AD patients showed more elevation of tau AIAs compared to tubulin. Our current results suggested that AIAs panel could be able to identify cases with neuro-degeneration when compared with healthy subjects. More interestingly, it is possible to differentiate between PD and AD cases through identifying specific AIAs profile for each neurodegenerative states.
    Matched MeSH terms: Tubulin/metabolism*
  5. Fulltext Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines
    Sim EU, Chan SL, Ng KL, Lee CW, Narayanan K
    Dis Markers, 2016;2016:5179594.
    PMID: 28018022 DOI: 10.1155/2016/5179594
    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.
    Matched MeSH terms: Tubulin/metabolism
  6. Effects of Nicotine and Tocotrienol-Rich Fraction Supplementation on Cytoskeletal Structures of Murine Pre-Implantation Embryos
    Hamirah NK, Kamsani YS, Mohamed Nor Khan NA, Ab Rahim S, Rajikin MH
    Med Sci Monit Basic Res, 2017 Dec 08;23:373-379.
    PMID: 29217815
    BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. The objective of this study was to evaluate the effects of nicotine, which is a source of oxidative stress, and subsequent supplementation with Tocotrienol-rich fraction (TRF) on actin and tubulin of 2- and 8-cell murine embryos. MATERIAL AND METHODS Thirty female Balb/C mice were divided into 4 groups: Group 1 received: subcutaneous (sc) injection of 0.9% NaCl; Group 2 received sc injection of 3.0 nicotine mg/kg bw/day; Group 3 received 3.0 sc injection of nicotine mg/kg bw/day +60 mg/kg bw/day TRF; and Group 4 received 60 sc injection of TRF mg/kg bw/day for 7 consecutive days. The animals were superovulated with 5 IU PMSG followed by 5 IU hCG 48 h later. Animals were cohabited with fertile males overnight and euthanized through cervical dislocation at 24 h post coitum. Embryos at the 2- and 8-cell stages were harvested, fixed, and stained to visualize actin and tubulin distributions by using CLSM. RESULTS Results showed that at 2-cell stage, actin intensities were significantly reduced in the nicotine group compared to that of the control group (p<0.001). In Group 3, the intensity of actin significantly increased compared to that of the nicotine group (p<0.001). At 8-cell stage, actin intensity of the nicotine group was significantly lower than that of the control group (p<0.001). The intensities of actin in Group 3 were increased compared to that of nicotine treatment alone (p<0.001). The same trend was seen in tubulin at 2- and 8-cell stages. Interestingly, both actin and tubulin structures in the TRF-treated groups were enhanced compared to the control. CONCLUSIONS This study suggests that TRF prevents the deleterious effects of nicotine on the cytoskeletal structures of 2- and 8-cell stages of pre-implantation mice embryos in vitro.
    Matched MeSH terms: Tubulin/drug effects
  7. Fulltext Cytoskeletal alterations in different developmental stages of in vivo cryopreserved preimplantation murine embryos
    Dasiman R, Rahman NS, Othman S, Mustafa MF, Yusoff NJ, Jusoff WH, et al.
    Med Sci Monit Basic Res, 2013 Oct 04;19:258-66.
    PMID: 24092420 DOI: 10.12659/MSMBR.884019
    BACKGROUND: This study aimed to investigate the effects of vitrification and slow freezing on actin, tubulin, and nuclei of in vivo preimplantation murine embryos at various developmental stages using a Confocal Laser Scanning Microscope (CLSM).

    MATERIAL/METHODS: Fifty female mice, aged 4-6 weeks, were used in this study. Animals were superovulated, cohabitated overnight, and sacrificed. Fallopian tubes were excised and flushed. Embryos at the 2-cell stage were collected and cultured to obtain 4- and 8-cell stages before being cryopreserved using vitrification and slow freezing. Fixed embryos were stained with fluorescence-labelled antibodies against actin and tubulin, as well as DAPI for staining the nucleus. Labelled embryos were scanned using CLSM and images were analyzed with Q-Win software V3.

    RESULTS: The fluorescence intensity of both vitrified and slow-frozen embryos was significantly lower for tubulin, actin, and nucleus as compared to non-cryopreserved embryos (p<0.001). Intensities of tubulin, actin, and nucleus in each stage were also decreased in vitrified and slow-frozen groups as compared to non-cryopreserved embryos.

    CONCLUSIONS: Cryopreservation of mouse embryos by slow freezing had a more detrimental effect on the actin, tubulin, and nucleus structure of the embryos compared to vitrification. Vitrification is therefore superior to slow freezing in terms of embryonic cryotolerance.

    Matched MeSH terms: Tubulin/metabolism
  8. Fulltext Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site
    Smedley CJ, Stanley PA, Qazzaz ME, Prota AE, Olieric N, Collins H, et al.
    Sci Rep, 2018 Jul 13;8(1):10617.
    PMID: 30006510 DOI: 10.1038/s41598-018-28880-2
    The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.
    Matched MeSH terms: Tubulin/metabolism*; Tubulin/chemistry; Tubulin Modulators/pharmacology
  9. Structure-activity relationship of polyisoprenyl benzophenones from Garcinia pyrifera on the tubulin/microtubule system
    Roux D, Hadi HA, Thoret S, Guénard D, Thoison O, Païs M, et al.
    J Nat Prod, 2000 Aug;63(8):1070-6.
    PMID: 10978200
    Microtubule disassembly inhibitory properties have been established for the known polyisoprenylated benzophenones xanthochymol (1a) and guttiferone E (1b). The compounds were isolated from the fruits of Garcinia pyrifera collected in Malaysia. A structure-activity relationship study, including natural and semisynthetic derivatives, delineated some structural features necessary for the interaction with tubulin within this compound class.
    Matched MeSH terms: Tubulin/analysis; Tubulin/biosynthesis
  10. Identification of a 48kDa tubulin or tubulin-like C6/36 mosquito cells protein that binds dengue virus 2 using mass spectrometry
    Chee HY, AbuBakar S
    Biochem Biophys Res Commun, 2004 Jul 16;320(1):11-7.
    PMID: 15207695
    Binding of dengue virus 2 (DENV-2) to C6/36 mosquito cells protein was investigated. A 48 kDa DENV-2-binding C6/36 cells protein (D2BP) was detected in a virus overlay protein-binding assay. The binding occurred only to the C6/36 cells cytosolic protein fraction and it was inhibited by free D2BP. D2BP was shown to bind to DENV-2 E in the far-Western-binding studies and using mass spectrometry (MS) and MS/MS, peptide masses of the D2BP that matched to beta-tubulin and alpha-tubulin chains were identified. These findings suggest that DENV-2 through DENV-2 E binds directly to a 48 kDa tubulin or tubulin-like protein of C6/36 mosquito cells.
    Matched MeSH terms: Tubulin/metabolism; Tubulin/chemistry*
  11. Synthesis of α,β-Unsaturated Carbonyl-Based Compounds, Oxime and Oxime Ether Analogs as Potential Anticancer Agents for Overcoming Cancer Multidrug Resistance by Modulation of Efflux Pumps in Tumor Cells
    Qin HL, Leng J, Zhang CP, Jantan I, Amjad MW, Sher M, et al.
    J Med Chem, 2016 Apr 14;59(7):3549-61.
    PMID: 27010345 DOI: 10.1021/acs.jmedchem.6b00276
    Sixty-nine novel α,β-unsaturated carbonyl based compounds, including cyclohexanone, tetralone, oxime, and oxime ether analogs, were synthesized. The antiproliferative activity determined by using seven different human cancer cell lines provided a structure-activity relationship. Compound 8ag exhibited high antiproliferative activity against Panc-1, PaCa-2, A-549, and PC-3 cell lines, with IC50 value of 0.02 μM, comparable to the positive control Erlotinib. The ten most active antiproliferative compounds were assessed for mechanistic effects on BRAF(V600E), EGFR TK kinases, and tubulin polymerization, and were investigated in vitro to reverse efflux-mediated resistance developed by cancer cells. Compound 8af exhibited the most potent BRAF(V600E) inhibitory activity with an IC50 value of 0.9 μM. Oxime analog 7o displayed the most potent EGFR TK inhibitory activity with an IC50 of 0.07 μM, which was analogous to the positive control. Some analogs including 7f, 8af, and 8ag showed a dual role as anticancer and MDR reversal agents.
    Matched MeSH terms: Tubulin
  12. Evaluation of ligustrazine based synthetic compounds for mechanism based antiproliferative effects
    Bukhari SNA, Alotaibi NH, Ahmad W, Alharbi KS, Abdelgawad MA, Al-Sanea MM, et al.
    Med Chem, 2020 Sep 05.
    PMID: 32888274 DOI: 10.2174/1573406416666200905125038
    BACKGROUND: Ligustrazine and chalcones have been reported previously for various biological activities including anticancer effects.

    OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine based chalcones, in current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on growth of five different types of cancer cells.

    METHODS: All compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.

    RESULTS: Majority of compounds exhibited strong inhibition of cancer cells especially synthetic compounds 4a and 4b bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in main structural backbone were found most powerful inhibitors of cancer cell growth. Most active 9 compounds among whole series were selected for further studies related to different cancer targets including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.

    CONCLUSION: Synthetic derivatives including 4a-b and 5a-b showed multitarget approach and showed strong inhibitory effects on EGFR, FAK and BRAF while three compounds including 3e bearing methoxy substitution, 4a and 4b with 1- pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.

    Matched MeSH terms: Tubulin
  13. First Report of Anthracnose Caused by Colletotrichum gloeosporioides on Soybean (Glycine max) in Malaysia
    Mahmodi F, Kadir JB, Wong MY, Nasehi A, Puteh A, Soleimani N
    Plant Dis, 2013 Jun;97(6):841.
    PMID: 30722625 DOI: 10.1094/PDIS-10-12-0944-PDN
    Soybean (Glycine max L.) is one of the most economically important crops in the world, and anthracnose is known to infect soybean in most countries. Colletotrichum truncatum is the common pathogen causing anthracnose of soybean. However, at least five species of Colletotrichum have been reported on soybean worldwide (2). In July 2010, anthracnose symptoms were observed on soybean in the experimental fields of the agriculture station in Ladang Dua, University Putra Malaysia located in Selangor state of Malaysia. Symptoms were initially observed on a few plants randomly within one field, but after 4 weeks, the disease was found in two additional fields scattered across an area of 1 km2. Pinkish-brown lesions were observed on the pods, and the formation of dark lesions on the leaves and stems was sometimes followed by stem girdling, dieback, and distorted growth. At later stages, numerous epidermal acervuli developed in the lesions, and mucilaginous conidial masses appeared during periods of high relative humidity. Conidia produced in acervuli were straight, cylindric, hyaline, and aseptate, with both ends rounded. Conidia measured (mean ± SD) 14.2 ± 0.6 × 3.6 ± 0.7 μm, and the L/W ratio was 3.95 μm. Six isolates of the fungus were obtained and identified as C. gloeosporioides on the basis of morphological characterization (3). The isolates were deposited in the University Putra of Malaysia Culture Collection (UPMCC). PDA cultures were white at first and subsequently became grayish to pink to reddish-brown. Amplification and sequence analysis of coding and none-coding regions of the ITS-rDNA (GenBank JX669450), actin (JX827430), β-tubulin (JX827454), histone (JX827448), chitin synthase (JX827436), and glyceraldehyde-3-phosphate dehydrogenase (JX827442) obtained from the representative isolate, CGM50, aligned with deposited sequences from GenBank and revealed 99 to 100% sequence identity with C. gloeosporioides strains (JX258757, JX009790, GQ849434, HM575301, JQ005413, and JX00948 from GenBank). One representative isolate, CGM50, was used for pathogenicity testing. Four non-infected detached leaves and pods of 24-day-old G. max var. Palmetto were surface-sterilized and inoculated by placing 10 μl of a conidial suspension (106 conidia ml-1) using either the wound/drop or non-wound/drop method (4), with 10 μl distilled water as a negative control. Leaves and pods were incubated at 25°C, 98% RH. The experiment was repeated twice. Five days after inoculation, the development of typical field symptoms, including acervuli formation, occurred on the leaves and pods of inoculated plants, but not on the negative controls. A fungus with the same colony and conidial morphology as CGM50 was recovered from the lesions on the inoculated leaves and pods. Anthracnose caused by C. gloeosporioides on soybean plants has been reported previously in different countries, but not in Malaysia (3). Geographically, the climate of Malaysia is highly conducive to maintain and cause outbreaks of anthracnose all year round; thus, the development of management recommendations will be inevitable for anthracnose control. To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on soybean in Malaysia. References: (1) U. Damm et al. Fungal Diversity 39:45, 2009. (2) S. L. Chen et al. J. Phytopathol. 154:654, 2006. (3) B. C. Sutton. The Genus Glomerella and its Anamorph Colletotrichum. CAB International, Wallingford, UK, 1992. (4) P. P. Than et al. Plant Pathol. 57:562, 2008. ERRATUM: A correction was made to this Disease Note on May 19, 2014. The author N. Soleimani was added.
    Matched MeSH terms: Tubulin
  14. First Report of Gliocephalotrichum bacillisporum Causing Fruit Rot of Rambutan (Nephelium lappaceum) in Malaysia
    Sakinah MAI, Latiffah Z
    Plant Dis, 2013 Aug;97(8):1110.
    PMID: 30722495 DOI: 10.1094/PDIS-09-12-0831-PDN
    Rambutan (Nephelium lappaceum L.) is among the tropical fruit grown in Malaysia and the demand for export rose in 2011. A fruit rot was observed between August and December 2011 from several areas in the states of Pulau Pinang and Perak, Malaysia. The symptoms initially appeared as light brown, water-soaked lesions that developed first in the pericarp and pulp, later enlarging and becoming dark brown. Greyish brown mycelia were observed on infected areas that turned yellowish at later stages of infection. Gliocephalotrichum bacillisporum was isolated from infected fruit by surface sterilization techniques. Conidia were mass-transferred onto potato dexstrose agar (PDA) plates and incubated at 27 ± 1°C. Tissue pieces (5 × 5 mm) excised from the margins between infected and healthy areas were then surface sterilized in 1% sodium hypochlorite for 3 to 5 min before being rinsed with distilled water, plated on PDA, and incubated at 27 ± 1°C for 7 days. Ten isolates of G. bacillisporum were obtained. Colonies on PDA were initially white before turning yellow with a feathery appearance. Microscopic characteristics on carnation leaf agar (CLA) consisted of hyaline conidia that were slightly ellipsoid to bacilliform with rounded apex ranging from 6.0 to 8.5 μm long and 2.0 to 2.5 μm wide. Conidiophores (70 to 130 μm long) were mostly single arising from large hypha approximately 13 to 16 μm. The conidiogenous structures were mostly quadriverticillate with dense, short, penicillate branches. The phialides were cylindrical and finger-like. Chlamydospores were present singly, in groups of 2 to 4, or in occasionally branched short chains and were brown in color with thick walls ranging from 11 to 13 μm. The cultural and morphological characteristics of G. bacillisporum isolates in the present study were very similar to previously published descriptions (1) except the conidiophores formed without sterile stipe extensions. All the G. bacillisporum isolates were deposited in culture collection at the Plant Pathology Lab, University Sains Malaysia, Penang. Molecular identification was accomplished from the ITS regions using ITS1 and ITS2 primers, and the β-tubulin gene using Bt2a and Bt2b primers (2). BLAST results from the ITS regions showed a 98 to 99% similarity with sequences of G. bacillisporum isolates reported in GenBank. Accession numbers of G. bacillisporum ITS regions: JX484850, JX484852, JX484853, JX484856, JX484858, JX484860, JX484862, JX484866, JX484867, and JX484868. The identity of G. bacillisporum isolates infecting rambutan was further confirmed by β-tubulin sequences (KC683909, KC683911, KC683912, KC683916, KC683919, KC683920, KC683923, KC683926, and KC683927), which showed 92 to 95% similarity with sequences of G. bacillisporum. Pathogenicity tests were also performed using mycelial plug (5 mm) and sprayed conidial suspensions (20 μl suspension of 106 conidia/ml) prepared from 7-day-old cultures. Inoculated fruits were incubated at 27 ± 1°C and after 10 days, similar rotting symptoms appeared on the fruit surface. The pathogen was reisolated from fruit rot lesions, thus fulfilling Koch's postulates, and tests were repeated twice. To our knowledge, this is the first report of G. bacillisporum causing fruit rot of rambutan (N. lappaceum L.) in Malaysia. References: (1) C. Decock et al. Mycologia 98:488, 2006. (2) N. L. Glass and G. C. Donaldson. Appl. Environ Microbiol. 61:1323, 1995.
    Matched MeSH terms: Tubulin
  15. First Report of Pestalotiopsis Leaf Blotch on Mangosteen in Hawaii
    Keith LM, Matsumoto TK
    Plant Dis, 2013 Jan;97(1):146.
    PMID: 30722309 DOI: 10.1094/PDIS-07-12-0702-PDN
    Mangosteen (Garcinia mangostana L.) is a tropical evergreen tree that produces one of the most prized tropical fruits, commonly known as the "Queen of the Fruits.″ Mangosteen has the potential to occupy a rapidly expanding niche market in Hawaii. In October 2009, a disease was observed that produced brown leaf spots and blotches surrounded by bright yellow halos at a mangosteen orchard located in Hakalau, Hawaii (19° 53' 49″ N, 155° 7' 35″ W). Recently transplanted 10+ year old trees were 95 to 100% infected. Pieces of infected leaves and stems were surface-sterilized, plated on potato dextrose agar (PDA), and incubated at 24°C ± 1°C for 21 days. The fungus growing on PDA was pale buff with sparse aerial mycelium and acervuli containing black, slimy spore masses. Single spore isolates were used for the morphological characteristics and molecular analysis. Conidia were 5-celled. Apical and basal cells were hyaline; the three median cells were umber to olivaceous. Conidia (n = 50) were 24.3 ± 0.2 × 7.5 ± 0.1 μm, with apical appendages, typically three, averaging 24.3 ± 0.4 μm long, and a basal appendage averaging 6.7 ± 0.2 μm long. DNA sequences were obtained from the β-tubulin gene and the internal transcribed spacer (ITS1 and ITS2) and 5.8S regions of the rDNA to confirm the identification. The morphological descriptions and measurements were similar to P. virgatula (Kleb.) Steyaert (1). Although sequence data of the ITS region (GenBank Accession No. JN542546) supports the identity of the fungus as P. virgatula, the taxonomy of this genus remains confused since there are only a few type cultures, so it is impossible to use sequences in GenBank to reliably clarify species names (2). To confirm pathogenicity, six leaves of two 3-year-old seedlings were inoculated. Seven-day-old cultures grown on 10% V8 agar at 24°C under continuous fluorescent lighting were used for inoculations. The inoculum consisted of spore suspensions in sterile distilled water adjusted to 6 × 105 conidia/ml. Using a fine haired paint brush, the inoculum was brushed onto the youngest leaves, while sterile distilled water was used as the control. The plants were incubated in a clear plastic bag placed on the laboratory bench at 24°C for 48 hours, then placed on a greenhouse bench and observed weekly for symptoms. After 14 days, leaf spots ranging in size from pinpoint to 5.4 mm in diameter with a distinctive yellow halo were present. Within 35 days, the leaf spots enlarged to leaf blotches ranging in size from 11.5 × 13.3 mm up to 28.3 × 34.6 mm with brown centers and a distinctive yellow halo identical to the field symptoms. A Pestalotiopsis sp. identical to that used to inoculate the seedlings was recovered from the leaf spots and blotches, confirming Koch's postulates. The experiment was repeated twice. Pestalotiopsis leaf blight has been reported in other countries growing mangosteen, including Thailand, Malaysia, and North Queensland, Australia (3). However, to our knowledge, this is the first report of a Pestalotiopsis sp. causing a disease on mangosteen in Hawaii. Although this disease is considered a minor problem in the literature (3), effective management practices should be established to avoid potential production losses. References: (1) E. F. Guba. Monograph of Pestalotia and Monochaetia. Harvard University Press, Cambridge, MA. 1961. (2) S. S. N. Maharachchikumbura et al. Fungal Div. 50:167, 2011. (3) R. C. Ploetz. Diseases of Tropical Fruit Crops. CABI Publishing. Wallingford, Oxfordshire, UK, 2003.
    Matched MeSH terms: Tubulin
  16. Discovery of gamma-mangostin from Garcinia mangostana as a potent and selective natural SIRT2 inhibitor
    Yeong KY, Khaw KY, Takahashi Y, Itoh Y, Murugaiyah V, Suzuki T
    Bioorg Chem, 2020 01;94:103403.
    PMID: 31711765 DOI: 10.1016/j.bioorg.2019.103403
    Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.
    Matched MeSH terms: Tubulin
  17. Occurrence of Anthracnose Caused by Colletotrichum truncatum on Chickpea (Cicer arietinum) in Malaysia
    Mahmodi F, Kadir JB, Nasehi A, Puteh A, Soleimani N
    Plant Dis, 2013 Nov;97(11):1507.
    PMID: 30708462 DOI: 10.1094/PDIS-03-13-0231-PDN
    At least nine Colletotrichum species, particularly Colletotrichum truncatum, have been recorded on legumes worldwide (1). In June 2010, samples of chickpea leaflets showing leaf spot disease symptoms were collected from experimental farms in Ladang Dua, Selangor state of Malaysia. Tan lesions with darker brown borders were observed on leaflets and were associated with premature leaf drop. Stem lesions initially appeared on the lower parts of stems and later progressed higher in the plant. Lesions often girdled the stem and caused severe dieback. Abundant acervuli developed in the lesions visible as black dots. Foliar lesions were removed, surface sterilized in 1% sodium hypochlorite for 2 min, rinsed twice with distilled water, dried on sterilized tissue paper, plated on PDA plates, and incubated at 25°C (3). Three isolates of the fungus were obtained and identified as C. truncatum on the basis of morphological characteristics (2). The isolates were deposited in the University Putra of Malaysia Culture Collection (UPMCC). Colony characteristics on PDA varied from greyish white to dark in color and exhibited mycelial growth with sparse acervuli. The isolates produced both sclerotia and setae in culture. Conidia (mean ± SD = 22 ± 0.83 × 3.6 ± 0.08 μm, L/W ratio = 6.1) produced in acervuli were falcate, hyaline, and aseptate, with tapering towards the acute and greatly curved apex. The conidial mass color varied from pale buff to saffron. Isolates produced simple to slightly lobed, mainly short clavate appressoria (mean ± SD = 9.60 ± 0.36 × 6.67 ± 0.29 μm, L/W ratio = 1.45). Amplification and sequence analysis of coding and none-coding regions of the ITS-rDNA (GenBank Accession JX971160), actin (JX975392), β-tubulin (KC109495), histone (KC109535), chitin synthase (KC109575), and glyceraldehyde-3-phosphate dehydrogenase (KC109615) obtained from the representative isolate, CTM37, aligned with deposited sequences from GenBank and revealed 99 to 100% sequence identity with C. truncatum strains (AJ301945, KC110827, GQ849442, GU228081, GU228359, and HM131501 from GenBank). Isolate CTM37 was used to test pathogenicity in the greenhouse. Five chickpea seeds of cultivar ILC-1929 were sown per pot in four replications. Ten days after seedling emergence, plants were inoculated with a spore suspension (concentration = 106 conidia ml-1) and check pots were sprayed with distilled water. After inoculation, the plants were covered with plastic bags for 48 h and kept at 28 to 33°C and >90% RH. After incubation, the plastic bags were removed and the plants were placed on greenhouse benches and monitored daily for symptom development (3). One week after inoculation, typical anthracnose symptoms developed on the leaves and stems of inoculated plants including acervuli formation, but not on the checks. A fungus with the same colony and conidial morphology as CTM37 was recovered from the lesions on the inoculated plants. The experiment was repeated twice. The ability to accurately diagnose Colletotrichum species is vital for the implementation of effective disease control and quarantine measures. We believe this is the first report of C. truncatum causing anthracnose on chickpea in Malaysia. References: (1) B. D. Gossen et al. Can. J. Plant Pathol. 31:65, 2009. (2) B. C. Sutton. The Genus Glomerella and its anamorph Colletotrichum. CAB International, Wallingford. UK. 1992. (3) P. P. Than et al. Plant Pathol. 57:562, 2008. ERRATUM: A correction was made to this Disease Note on May 19, 2014. The author N. Soleimani was added.
    Matched MeSH terms: Tubulin
  18. Impact of UV radiation on Mxene-mediated tubulin dissociation and mitochondrial apoptosis in breast cancer cells
    Tan EW, Simon SE, Numan A, Khalid M, Tan KO
    Colloids Surf B Biointerfaces, 2024 Mar;235:113793.
    PMID: 38364521 DOI: 10.1016/j.colsurfb.2024.113793
    Breast cancer is a global health concern that requires personalized therapies to prevent relapses, as conventional treatments may develop resistance over time. Photothermal therapy using spectral radiation or intense light emission is a broad-spectrum treatment that induces hyperthermia-mediated cancer cell death. MXene, a two-dimensional material, has been reported to have potential biological applications in photothermal therapy for cancer treatment. In this study, we investigated the apoptotic activity of MXene and UV-irradiated MXene in MCF-7 breast cancer cells by treating them with varying concentrations of MXene. The cytotoxicity of MXene and UV was evaluated by analyzing cellular morphology, nuclei condensation, caspase activation, and apoptotic cell death. We also assessed the effect of the combined treatment on the expression and cellular distribution of Tubulin, a key component of microtubules required for cell division. At low concentrations of MXene (up to 100 µg/ml), the level of cytotoxicity in MCF-7 cells was low. However, the combined treatment of MXene and UV resulted in a synergistic increase in cytotoxicity, causing rounded cellular morphology, condensed nuclei, caspase activation, and apoptotic cell death. Furthermore, the treatment reduced Tubulin protein expression and cellular distribution, indicating a potent inducer of cell death with potential application for cancer treatment. The study demonstrates that the combined treatment of MXene and UVB irradiation is a promising strategy for inducing apoptotic cell death in breast cancer cells, suggesting its potential as a therapeutic intervention for breast cancer.
    Matched MeSH terms: Tubulin
  19. Fulltext EphrinB2 signalling modulates the neural differentiation of human dental pulp stem cells
    Heng BC, Gong T, Xu J, Lim LW, Zhang C
    Biomed Rep, 2018 Aug;9(2):161-168.
    PMID: 29963307 DOI: 10.3892/br.2018.1108
    Dental pulp stem cells (DPSCs) originate from the embryonic neural crest and have neurogenic potential. The present study investigated the roles of the forward and reverse EphrinB2 signalling pathways during DPSC neurogenesis. Treatment of DPSCs with recombinant EphrinB2-Fc protein over 7 days in a neural induction culture resulted in significant downregulation of the following neural markers: βIII-Tubulin, neural cell adhesion molecule (NCAM), nestin, neurogenin 2 (NGN2), neurofilament medium polypeptide and Musashi1. Immunocytochemistry revealed that EphrinB2-Fc-treated DPSCs exhibited more rounded morphologies with fewer neurite outgrowths as well as reduced protein expression of βIII-tubulin and NGN2. Treatment of DPSCs with a peptide inhibitor specific to the EphB4 receptor significantly upregulated expression of the neural markers microtubule-associated protein 2, Musashi1, NGN2 and neuron-specific enolase, whereas treatment with a peptide inhibitor specific to the EphB2 receptor exerted negligible effects on neurogenesis. Transgenic expression of EphrinB2 in DPSCs resulted in significant upregulation of Musashi1 and NCAM gene expression, while treatment of DPSCs with recombinant EphB4-Fc protein led to significant upregulation of only Musashi1. Thus, it may be concluded that stimulation of forward EphrinB2-EphB4 signalling markedly inhibited neurogenesis in DPSCs, whereas suppression of this forward signalling pathway with peptide inhibitor specific to EphB4 promoted neurogenesis. Meanwhile, stimulation of reverse EphB4-EphrinB2 signalling only marginally enhanced the neural differentiation of DPSCs. The present findings indicate the potential application of peptide or small molecule inhibitors of EphrinB2 forward signalling in neural tissue engineering with DPSCs.
    Matched MeSH terms: Tubulin
  20. Antimitotic and cytotoxic flavonols from Zieridium pseudobtusifolium and Acronychia porteri
    Lichius JJ, Thoison O, Montagnac A, Païs M, Guéritte-Voegelein F, Sévenet T, et al.
    J Nat Prod, 1994 Jul;57(7):1012-6.
    PMID: 7964782
    Bioassay-guided fractionation of the extracts of Zieridium pseudobtusifolium and Acronychia porteri led to the isolation of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], which showed activity against (KB) human nasopharyngeal carcinoma cells (IC50 0.04 micrograms/ml) and inhibited tubulin assembly into microtubules (IC50 12 microM). Two other known flavonols, digicitrin [2] and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone [5], were also isolated together with three new ones, 3-O-demethyldigicitrin [3], 3,5,3'-trihydroxy-6,7,8,4'-tetramethoxyflavone [4], and 3,5-dihydroxy-6,7,8,3',4'-pentamethoxyflavone [6]. All of these flavonols showed cytotoxic activity against KB cells.
    Matched MeSH terms: Tubulin/metabolism
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